Iron levels in the human brain: A post-mortem study of anatomical region differences and age-related changes

Abstract

The link between brain iron homeostasis and neurodegenerative disease has been the subject of extensive research. There is increasing evidence of iron accumulation during ageing, and altered iron levels in some specific brain regions in neurodegenerative disease patients have been reported. Using graphite furnace atomic absorption spectrometry after microwave-assisted acid digestion of the samples, iron levels were determined in 14 different areas of the human brain [frontal cortex, superior and middle temporal, caudate nucleus, putamen, globus pallidus, cingulated gyrus, hippocampus, inferior parietal lobule, visual cortex of the occipital lobe, midbrain, pons (locus coeruleus), medulla and cerebellum (dentate nucleus)] of n=42 adult individuals (71±12 years old, range: 53-101 years old) with no known history or evidence of neurodegenerative, neurological or psychiatric disorders. It was found that the iron distribution in the adult human brain is quite heterogeneous. The highest levels were found in the putamen (mean±SD, range: 855±295μg/g, 304-1628μg/g) and globus pallidus (739±390μg/g, 225-1870μg/g), and the lowest levels were observed in the pons (98±43μg/g, 11-253μg/g) and medulla (56±25μg/g, 13-115μg/g). Globally, iron levels proved to be age-related. The positive correlation between iron levels and age was most significant in the basal ganglia (caudate nucleus, putamen and globus pallidus). Compared with the age-matched control group, altered iron levels were observed in specific brain areas of one Parkinson's disease patient (the basal ganglia) and two Alzheimer's disease patients (the hippocampus).

High-resolution characterisation of the aging brain using simultaneous quantitative susceptibility mapping (QSM) and R2* measurements at 7 T

“…10 and Table 2), which are consistent with previous in vivo MRI Li et al, 2014;Poynton et al, 2015;Rodrigue et al, 2013;AcostaCabronero et al 2016) and post-mortem iron analyses (Hallgren and Sourander, 1958;Ramos et al, 2014). Furthermore, the findings presented here also agree with the aforementioned studies in that independent of age, the basal ganglia system, RN and cerebellar DN contain more iron than the thalamus, hippocampus, amygdala, isocortex and WM.…”

Age and sex related differences in subcortical brain iron concentrations among healthy adults

“…Non-heme iron can only be studied directly postmortem (Hallgren & Sourander, 1958; Morris, Candy, Oakley, Bloxham, & Edwardson, 1992; Ramos et al, 2014; Ward et al, 2014), while in-vivo magnetic resonance imaging (MRI) can estimate iron deposits based on the interplay between its paramagnetic properties and the proton relaxation resonance behavior of tissue water (Schenck, 2003). Most of the non-heme iron in the brain affecting the MRI signal is believed to be consisting of ferritin and hemosiderin (Schenck, 2003; Schenck & Zimmerman, 2004).…”

“…Pre-menstrual blood loss reduces peripheral iron levels in women and may contribute to sex differences in brain iron accumulation (Tischler et al, 2012; Whitfield et al, 2003). Women had lower levels of brain iron compared to men from midlife to old age according to a recent histologic report (Ramos et al, 2014). Sex steroids, whose levels change post menopause (Al-Azzawi & Palacios, 2009), may also influence sex related variations of brain iron levels (Gu, Xi, Liu, Keep, & Hua, 2010).…”

Haemochromatosis and dementia: cause or contributor?

“…15,16 Increased iron deposition has been found, especially in the hippocampus, in some cases of AD. 17 Post-mortem studies have indicated that the brain stores more iron as it ages and imaging studies by Bartzokis and others have shown increased levels of iron in the hippocampus and basal ganglia of patients with AD, PD and Huntington's disease. 18 The very rapid cognitive decline in our case could be linked with iron deposition.…”